"Our long-term goals are to develop recombinant avirulent Salmonella vaccines for oral administration, protecting humans against bacterial, viral mycotic and parasitic pathogens. This delivery system is being developed for synthesis of gamete-specific antigens, to block fertilization, and tumor antigens, to halt cancers. Augmentation and/or modulation of the immune response to foreign antigens delivered by Salmonella is being accomplished by constructing strains that also express genes for cytokines. Immunization with Salmonella vaccines introduces the potential for fecal shedding of the bacteria into the environment, possibly leading to immunization of unintended individuals. The objective of the Phase I study is to design, construct and evaluate biological containment strategies so that live vaccine strains are unable to survive and proliferate in the environment. The objectives during the Phase II study will be to construct and assess additional biological containment strategies to reinforce the primary containment strategies. These vaccine constructs will be fully evaluated for the induction of protective immunity following vaccination of animals, including human volunteers, and for their survival in various environments likely to be encountered in nature. Recombinant avirulent S. typhimurium strains will be tested in mice and recombinant avirulent S. typhi and S. paratyphi strains evaluated in human volunteers."